Role and significance of virus-bacteria interactions in disease progression.

Understanding disease pathogenesis caused by bacteria/virus, from the perspective of individual pathogen has provided meaningful insights. However, as viral and bacterial counterparts might inhabit the same infection site, it becomes crucial to consider their interactions and contributions in disease onset and progression. The objective of the review is to highlight the importance of considering both viral and bacterial agents during the course of coinfection. The review provides a unique perspective on the general theme of virus-bacteria interactions, which either lead to colocalized infections that are restricted to one anatomical niche, or systemic infections that have a systemic effect on the human host. The sequence, nature, and underlying mechanisms of certain virus-bacteria interactions have been elaborated with relevant examples from literature. It also attempts to address the various applied aspects, including diagnostic and therapeutic strategies for individual infections as well as virus-bacteria coinfections. The review aims to aid researchers in comprehending the intricate interplay between virus and bacteria in disease progression, thereby enhancing understanding of current methodologies and empowering the development of novel health care strategies to tackle coinfections.

BactInt: A domain driven transfer learning approach for extracting inter-bacterial associations from biomedical text.

BACKGROUND: The healthy as well as dysbiotic state of an ecosystem like human body is known to be influenced not only by the presence of the bacterial groups in it, but also with respect to the associations within themselves. Evidence reported in biomedical text serves as a reliable source for identifying and ascertaining such inter bacterial associations. However, the complexity of the reported text as well as the ever-increasing volume of information necessitates development of methods for automated and accurate extraction of such knowledge. METHODS: A BioBERT (biomedical domain specific language model) based information extraction model for bacterial associations is presented that utilizes learning patterns from other publicly available datasets. Additionally, a specialized sentence corpus has been developed to significantly improve the prediction accuracy of the 'transfer learned' model using a fine-tuning approach. RESULTS: The final model was seen to outperform all other variations (non-transfer learned and non-fine-tuned models) as well as models trained on BioGPT (a domain trained Generative Pre-trained Transformer). To further demonstrate the utility, a case study was performed using bacterial association network data obtained from experimental studies. CONCLUSION: This study attempts to demonstrate the applicability of transfer learning in a niche field of life sciences where understanding of inter bacterial relationships is crucial to obtain meaningful insights in comprehending microbial community structures across different ecosystems. The study further discusses how such a model can be further improved by fine tuning using limited training data. The results presented and the datasets made available are expected to be a valuable addition in the field of medical informatics and bioinformatics.

NetSets.js: a JavaScript framework for compositional assessment and comparison of biological networks through Venn-integrated network diagrams.

MOTIVATION: Venn diagrams are frequently used to compare composition of datasets (e.g. datasets containing list of proteins and genes). Network diagram constructed using such datasets are usually generated using 'list of edges', popularly known as edge-lists. An edge-list and the corresponding generated network are, however, composed of two elements, namely, edges (e.g. protein-protein interactions) and nodes (e.g. proteins). Researchers often use individual lists of edges and nodes to compare composition of biological networks using existing Venn diagram tools. However, specialized analysis workflows are required for comparison of nodes as well as edges. Apart from this, different tools or graph libraries are needed for visualizing any specific edges of interest (e.g. protein-protein interactions which are present across all networks or are shared between subset of networks or are exclusively present in a selected network). Further, these results are required to be exported in the form of publication worthy network diagram(s), particularly for small networks. RESULTS: We introduce a (server independent) JavaScript framework (called NetSets.js) that integrates popular Venn and network diagrams in a single application. A free to use intuitive web application (utilizing NetSets.js), specifically designed to perform both compositional comparisons (e.g. for identifying common/exclusive edges or nodes) and interactive user defined visualizations of network (for the identified common/exclusive interactions across multiple networks) using simple edge-lists is also presented. The tool also enables connection to Cytoscape desktop application using the Netsets-Cyapp. We demonstrate the utility of our tool using real world biological networks (microbiome, gene interaction, multiplex and protein-protein interaction networks). AVAILABILITYAND IMPLEMENTATION: http://web.rniapps.net/netsets (freely available for academic use). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Corrigendum: 'TIME': A Web Application for Obtaining Insights into Microbial Ecology Using Longitudinal Microbiome Data.

[This corrects the article DOI: 10.3389/fmicb.2018.00036.].

Corrigendum: FLIM-MAP: Gene Context Based Identification of Functional Modules in Bacterial Metabolic Pathways.

[This corrects the article DOI: 10.3389/fmicb.2018.02183.].

Correction to: Visual exploration of microbiome data.

Correction to: J Biosci (2019) 44:119 https://doi.org/10.1007/s12038-019-9933-z In the October 2019 Special Issue of the Journal of Biosciences on Current Trends in Microbiome Research, in the Review article titled "Visual exploration of microbiome data" by Bhusan K. Kuntal and Sharmila S. Mande (DOI: 10.1007/s12038-019-9933-z; Vol. 44, Article No. 119), affiliation 3 for Bhusan K. Kuntal was incorrectly mentioned as "Academy of Scientific and Innovative Research, CSIR-National Chemical Laboratory Campus, Pune 411008, India''. The correct affiliation should read as ''Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India".

Corrigendum: "EviMass": A Literature Evidence-Based Miner for Human Microbial Associations.

[This corrects the article DOI: 10.3389/fgene.2019.00849.].

Correction to: NetConfer: a web application for comparative analysis of multiple biological networks.

An amendment to this paper has been published and can be accessed via the original article.

NetConfer: a web application for comparative analysis of multiple biological networks.

BACKGROUND: Most biological experiments are inherently designed to compare changes or transitions of state between conditions of interest. The advancements in data intensive research have in particular elevated the need for resources and tools enabling comparative analysis of biological data. The complexity of biological systems and the interactions of their various components, such as genes, proteins, taxa, and metabolites, have been inferred, represented, and visualized via graph theory-based networks. Comparisons of multiple networks can help in identifying variations across different biological systems, thereby providing additional insights. However, while a number of online and stand-alone tools exist for generating, analyzing, and visualizing individual biological networks, the utility to batch process and comprehensively compare multiple networks is limited. RESULTS: Here, we present a graphical user interface (GUI)-based web application which implements multiple network comparison methodologies and presents them in the form of organized analysis workflows. Dedicated comparative visualization modules are provided to the end-users for obtaining easy to comprehend, insightful, and meaningful comparisons of various biological networks. We demonstrate the utility and power of our tool using publicly available microbial and gene expression data. CONCLUSION: NetConfer tool is developed keeping in mind the requirements of researchers working in the field of biological data analysis with limited programming expertise. It is also expected to be useful for advanced users from biological as well as other domains (working with association networks), benefiting from provided ready-made workflows, as they allow to focus directly on the results without worrying about the implementation. While the web version allows using this application without installation and dependency requirements, a stand-alone version has also been supplemented to accommodate the offline requirement of processing large networks.

FunGeCo: a web-based tool for estimation of functional potential of bacterial genomes and microbiomes using gene context information.

MOTIVATION: Functional potential of genomes and metagenomes which are inferred using homology-based methods are often subjected to certain limitations, especially for proteins with homologs which function in multiple pathways. Augmenting the homology information with genomic location of the constituent genes can significantly improve the accuracy of estimated functions. This can help in distinguishing cognate homolog belonging to a candidate pathway from its other homologs functional in different pathways. RESULTS: In this article, we present a web-based analysis platform 'FunGeCo' to enable gene-context-based functional inference for microbial genomes and metagenomes. It is expected to be a valuable resource and complement the existing tools for understanding the functional potential of microbes which reside in an environment. AVAILABILITY AND IMPLEMENTATION: https://web.rniapps.net/fungeco [Freely available for academic use]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Corrigendum: Web-gLV: A Web Based Platform for Lotka-Volterra Based Modeling and Simulation of Microbial Populations.

[This corrects the article DOI: 10.3389/fmicb.2019.00288.].

Visual exploration of microbiome data.

A dramatic increase in large-scale cross-sectional and temporal-level metagenomic experiments has led to an improved understanding of the microbiome and its role in human well-being. Consequently, a plethora of analytical methods has been developed to decipher microbial biomarkers for various diseases, cluster different ecosystems based on microbial content, and infer functional potential of the microbiome as well as analyze its temporal behavior. Development of user-friendly visualization methods and frameworks is necessary to analyze this data and infer taxonomic and functional patterns corresponding to a phenotype. Thus, new methods as well as application of pre-existing ones has gained importance in recent times pertaining to the huge volume of the generated microbiome data. In this review, we present a brief overview of some useful visualization techniques that have significantly enriched microbiome data analytics.

Correction to: CompNet: a GUI based tool for comparison of multiple biological interaction networks.

Following publication of the original article [1], the authors requested to update a link in the article. There was a server update and the hosted applications needed to move to a new web location.

"EviMass": A Literature Evidence-Based Miner for Human Microbial Associations.

The importance of understanding microbe-microbe as well as microbe-disease associations is one of the key thrust areas in human microbiome research. High-throughput metagenomic and transcriptomic projects have fueled discovery of a number of new microbial associations. Consequently, a plethora of information is being added routinely to biomedical literature, thereby contributing toward enhancing our knowledge on microbial associations. In this communication, we present a tool called "EviMass" (Evidence based mining of human Microbial Associations), which can assist biologists to validate their predicted hypotheses from new microbiome studies. Users can interactively query the processed back-end database for microbe-microbe and disease-microbe associations. The EviMass tool can also be used to upload microbial association networks generated from a human "disease-control" microbiome study and validate the associations from biomedical literature. Additionally, a list of differentially abundant microbes for the corresponding disease can be queried in the tool for reported evidences. The results are presented as graphical plots, tabulated summary, and other evidence statistics. EviMass is a comprehensive platform and is expected to enable microbiome researchers not only in mining microbial associations, but also enriching a new research hypothesis. The tool is available free for academic use at https://web.rniapps.net/evimass.

Web-gLV: A Web Based Platform for Lotka-Volterra Based Modeling and Simulation of Microbial Populations.

The affordability of high throughput DNA sequencing has allowed us to explore the dynamics of microbial populations in various ecosystems. Mathematical modeling and simulation of such microbiome time series data can help in getting better understanding of bacterial communities. In this paper, we present Web-gLV-a GUI based interactive platform for generalized Lotka-Volterra (gLV) based modeling and simulation of microbial populations. The tool can be used to generate the mathematical models with automatic estimation of parameters and use them to predict future trajectories using numerical simulations. We also demonstrate the utility of our tool on few publicly available datasets. The case studies demonstrate the ease with which the current tool can be used by biologists to model bacterial populations and simulate their dynamics to get biological insights. We expect Web-gLV to be a valuable contribution in the field of ecological modeling and metagenomic systems biology.

'NetShift': a methodology for understanding 'driver microbes' from healthy and disease microbiome datasets.

The combined effect of mutual association within the co-inhabiting microbes in human body is known to play a major role in determining health status of individuals. The differential taxonomic abundance between healthy and disease are often used to identify microbial markers. However, in order to make a microbial community based inference, it is important not only to consider microbial abundances, but also to quantify the changes observed among inter microbial associations. In the present study, we introduce a method called 'NetShift' to quantify rewiring and community changes in microbial association networks between healthy and disease. Additionally, we devise a score to identify important microbial taxa which serve as 'drivers' from the healthy to disease. We demonstrate the validity of our score on a number of scenarios and apply our methodology on two real world metagenomic datasets. The 'NetShift' methodology is also implemented as a web-based application available at https://web.rniapps.net/netshift.

FLIM-MAP: Gene Context Based Identification of Functional Modules in Bacterial Metabolic Pathways.

Prediction of functional potential of bacteria can only be ascertained by the accurate annotation of its metabolic pathways. Homology based methods decipher metabolic gene content but ignore the fact that homologs of same protein can function in different pathways. Therefore, mere presence of all constituent genes in an organism is not sufficient to indicate a pathway. Contextual occurrence of genes belonging to a pathway on the bacterial genome can hence be exploited for an accurate estimation of functional potential of a bacterium. In this communication, we present a novel annotation resource to accurately identify pathway presence by using gene context. Our tool FLIM-MAP (Functionally Important Modules in bacterial Metabolic Pathways) predicts biologically relevant functional units called 'GCMs' (Gene Context based Modules) from a given metabolic reaction network. We benchmark the accuracy of our tool on amino acids and carbohydrate metabolism pathways.

'TIME': A Web Application for Obtaining Insights into Microbial Ecology Using Longitudinal Microbiome Data.

Realization of the importance of microbiome studies, coupled with the decreasing sequencing cost, has led to the exponential growth of microbiome data. A number of these microbiome studies have focused on understanding changes in the microbial community over time. Such longitudinal microbiome studies have the potential to offer unique insights pertaining to the microbial social networks as well as their responses to perturbations. In this communication, we introduce a web based framework called 'TIME' (Temporal Insights into Microbial Ecology'), developed specifically to obtain meaningful insights from microbiome time series data. The TIME web-server is designed to accept a wide range of popular formats as input with options to preprocess and filter the data. Multiple samples, defined by a series of longitudinal time points along with their metadata information, can be compared in order to interactively visualize the temporal variations. In addition to standard microbiome data analytics, the web server implements popular time series analysis methods like Dynamic time warping, Granger causality and Dickey Fuller test to generate interactive layouts for facilitating easy biological inferences. Apart from this, a new metric for comparing metagenomic time series data has been introduced to effectively visualize the similarities/differences in the trends of the resident microbial groups. Augmenting the visualizations with the stationarity information pertaining to the microbial groups is utilized to predict the microbial competition as well as community structure. Additionally, the 'causality graph analysis' module incorporated in TIME allows predicting taxa that might have a higher influence on community structure in different conditions. TIME also allows users to easily identify potential taxonomic markers from a longitudinal microbiome analysis. We illustrate the utility of the web-server features on a few published time series microbiome data and demonstrate the ease with which it can be used to perform complex analysis.

Web-igloo: a web based platform for multivariate data visualization.

Motivation: The majority of data generated routinely from various experiments are essentially multivariate, often categorized with multiple experimental metadata. Analyzing such results with interactive visualizations often yields interesting and intuitive results which otherwise remains undisclosed. Results: In this paper, we present Web-Igloo-a GUI based interactive 'feature decomposition independent' multivariate data visualization platform. Web-Igloo is likely to be a valuable contribution in the field of visual data mining, especially for researchers working with but not limited to multi-omics data. To demonstrate its utility, we have used a metagenomic dataset pertaining to the effect of multiple doses of antibiotic treatment on the human gut microbiome. Availability and Implementation: http://metagenomics.atc.tcs.com/webigloo and http://121.241.184.233/webigloo [Freely available for academic use]. Contact: sharmila@atc.tcs.com. Supplementary information: Supplementary data are available at Bioinformatics online.

CompNet: a GUI based tool for comparison of multiple biological interaction networks.

BACKGROUND: Network visualization and analysis tools aid in better understanding of complex biological systems. Furthermore, to understand the differences in behaviour of system(s) under various environmental conditions (e.g. stress, infection), comparing multiple networks becomes necessary. Such comparisons between multiple networks may help in asserting causation and in identifying key components of the studied biological system(s). Although many available network comparison methods exist, which employ techniques like network alignment and querying to compute pair-wise similarity between selected networks, most of them have limited features with respect to interactive visual comparison of multiple networks. RESULTS: In this paper, we present CompNet - a graphical user interface based network comparison tool, which allows visual comparison of multiple networks based on various network metrics. CompNet allows interactive visualization of the union, intersection and/or complement regions of a selected set of networks. Different visualization features (e.g. pie-nodes, edge-pie matrix, etc.) aid in easy identification of the key nodes/interactions and their significance across the compared networks. The tool also allows one to perform network comparisons on the basis of neighbourhood architecture of constituent nodes and community compositions, a feature particularly useful while analyzing biological networks. To demonstrate the utility of CompNet, we have compared a (time-series) human gene-expression dataset, post-infection by two strains of Mycobacterium tuberculosis, overlaid on the human protein-protein interaction network. Using various functionalities of CompNet not only allowed us to comprehend changes in interaction patterns over the course of infection, but also helped in inferring the probable fates of the host cells upon infection by the two strains. CONCLUSIONS: CompNet is expected to be a valuable visual data mining tool and is freely available for academic use from http://metagenomics.atc.tcs.com/compnet/ or http://121.241.184.233/compnet/.